Clinical Research Directory

Genomic and Phenotypic Diversity of Carbapenemase-producing Escherichia Coli Strains Circulating in Southern France

Carbapenemase-producing Enterobacteriaceae (CPE) are classified as emerging Highly Resistant Bacteria (eHRB) because they expose infected patients to the risk of treatment failure due to the strains' resistance to last-line β-lactams, carbapenems, and frequent co-resistance to other classes of antibiotics, leading to increased morbidity and mortality. Their high epidemiogenic potential has enabled their global spread. In France, the incidence of Carbapenemase-producing Enterobacteriaceae is rising sharply, both in colonization and in infections. Parallel to this increase, Escherichia coli has become the most common Carbapenemase-producing Enterobacteriaceae (35% of strains in 2024, National Research Committee data), surpassing Klebsiella pneumoniae (24%). The investigators hypothesize that the increase in the prevalence of carbapenemase-producing Echerichia coli is associated with a diversification of clones, enzymes, and their variants, and may pose a threefold threat: i) the spread of genes encoding carbapenemases within pathogenic extraintestinal Echerichia coli (ExPEC) pathogroups responsible for urinary tract infections and bacteremias, with a high risk of resistance spreading in the community, ii) the silent spread of Echerichia coli strains producing OXA-48 variants with reduced carbapenem hydrolytic activity, OXA-244 and OXA-484, which are not detected or poorly detected by conventionally used screening media and iii) the emergence of New Dehli Metallo-beta-lactamase (NDM) variants with high hydrolytic activity, such as NDM-5, within Echerichia coli clones possessing Penicillin-Binding Proteins (PLPs) with low affinity for antibiotics, leading to very high-level resistance and a therapeutic dead end in infected patients.

Probiotic Delivered to the Small Intestine Changes Microbiota

This study will determine whether encapsulation of probiotic bacteria using natural plant protein can enhance bacterial colonisation. Lactobacillus rhamnosus is an ideal strain for the intervention, as it has been shown to affect overall gut health, gut-brain axis, and brain function. Participants aged 25 to 65 years will be recruited and assessed on four occasions to compare the effects of the blood chemicals and bacterial composition in faeces of a 28-day ingestion of a yoghurt beverage with and without the probiotic strain of interest. The study window will be 70+/13 days. This study will provide important information regarding the physiological function of probiotics in the small intestine. Understanding the underlying physiological effects of targeted probiotic delivery to the intestine and the impact on the microbiome is important for health outcomes.

Predictive Score in Patients With Hematological Malignancies Colonized by Multidrug-resistant Enterobacteriaceae

The goals of this observational study are to identify risk factors for ESBL-producing Enterobacterales and carbapenemase-producing Enterobacterales (CPE) colonization in oncohematological patients with severe neutropenia, and to develop and validate a predictive model of infection caused by ESBL-producing Enterobacterales and CPE in patients previously colonized by the same bacteria. The main questions the study aims to answer are: * What are the risk factors for ESBL-producing Enterobacterales and CPE colonization in patients with severe neutropenia? * Can a predictive model be developed to accurately predict infections in the colonized patients? Study Design \& Participants: Participants will be screened after receiving neutropenia-inducing treatment (e.g., chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy, or others). A baseline rectal swab will be collected to assess initial colonization status, followed by weekly swabs throughout the duration of neutropenia. Patients will be followed for 90 days from initial screening, during which the study team will record any infections, with an additional 30-day follow-up period. All hospitalization data will be recorded.